RGD Reference Report - Reduced expression of dentin sialophosphoprotein is associated with dysplastic dentin in mice overexpressing transforming growth factor-beta 1 in teeth. - Rat Genome Database

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Reduced expression of dentin sialophosphoprotein is associated with dysplastic dentin in mice overexpressing transforming growth factor-beta 1 in teeth.

Authors: Thyagarajan, T  Sreenath, T  Cho, A  Wright, JT  Kulkarni, AB 
Citation: Thyagarajan T, etal., J Biol Chem 2001 Apr 6;276(14):11016-20. Epub 2000 Dec 14.
RGD ID: 734904
Pubmed: PMID:11116156   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M010502200   (Journal Full-text)

Transforming growth factor (TGF)-beta1 is expressed in developing tooth from the initiation stage through adulthood. Odontoblast-specific expression of TGF-beta1 in the tooth continues throughout life; however, the precise biological functions of this growth factor in the odontoblasts are not clearly understood. Herein, we describe the generation of transgenic mice that overexpress active TGF-beta1 predominantly in the odontoblasts. Teeth of these mice show a significant reduction in the tooth mineralization, defective dentin formation, and a relatively high branching of dentinal tubules. Dentin extracellular matrix components such as type I and III collagens are increased and deposited abnormally in the dental pulp, similar to the hereditary human tooth disorders such as dentin dysplasia and dentinogenesis imperfecta. Calcium, one of the crucial inorganic components of mineralization, is also apparently increased in the transgenic mouse teeth. Most importantly, the expression of dentin sialophosphoprotein (dspp), a candidate gene implicated in dentinogenesis imperfecta II (MIM 125420), is significantly down-regulated in the transgenic teeth. Our results provide in vivo evidence suggesting that TGF-beta1 mediated expression of dspp is crucial for dentin mineralization. These findings also provide for the first time a direct experimental evidence indicating that decreased dspp gene expression along with the other cellular changes in odontoblasts may result in human hereditary dental disorders like dentinogenesis imperfecta II (MIM 125420) and dentin dysplasia (MIM 125400 and 125420).



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DSPPHumandentin dysplasia  ISODspp (Mus musculus)mRNA:decreased expression:incisor and molar (mouse)RGD 
DsppRatdentin dysplasia  ISODspp (Mus musculus)mRNA:decreased expression:incisor and molar (mouse)RGD 
DsppMousedentin dysplasia  IEP mRNA:decreased expression:incisor and molar (mouse)RGD 
DSPPHumandentinogenesis imperfecta  ISODspp (Mus musculus)mRNA:decreased expression:incisor and molar (mouse)RGD 
DsppRatdentinogenesis imperfecta  ISODspp (Mus musculus)mRNA:decreased expression:incisor and molar (mouse)RGD 
DsppMousedentinogenesis imperfecta  IEP mRNA:decreased expression:incisor and molar (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dspp  (dentin sialophosphoprotein)

Genes (Mus musculus)
Dspp  (dentin sialophosphoprotein)

Genes (Homo sapiens)
DSPP  (dentin sialophosphoprotein)

Objects referenced in this article
Gene TGFB1 transforming growth factor beta 1 Homo sapiens
Gene Tgfb1 transforming growth factor, beta 1 Rattus norvegicus

Additional Information